A closer look at an ezetimibe discussion

Author’s response:

Thank you, Dr. Crump, for your feedback. I suspect that most clinicians would welcome more robust outcomes data on ezetimibe, but to date none have been published.

The IMPROVE-IT trial¹ offers the best supportive evidence for the use of ezetimibe, but still finds only a 2% absolute risk reduction (ARR) in a composite endpoint (cardiovascular death, nonfatal myocardial infarction, unstable angina requiring rehospitalization, coronary revascularization ≥30 days after randomization, or nonfatal stroke), equating to a number needed to treat (NNT) of 50.

Most clinicians would welcome more robust outcomes data on ezetimibe, but to date none have been published.

The largest meta-analysis of ezetimibe trials—published prior to IMPROVE-IT—combined 31,048 patients to find an ARR for myocardial infarction of 1.1% (NNT=91) and an ARR for stroke of 0.6% (NNT=167), with no difference in cardiovascular death.²

Because of its limited outcomes data, ezetimibe is best reserved for patients unable to tolerate statin therapy, for those in whom statin therapy is contraindicated, or for those not meeting LDL-C reduction goals with a statin alone. This position is also supported by the United Kingdom’s National Institute for Health and Care Excellence (NICE).³

Finally, you are correct that the 2013 American College of Cardiology/American Heart Association Guideline on the Assessment of Cardiovascular Risk does not advocate a number-driven LDL-C goal, but rather recommends a risk-based moderate (30%-50%) or high-intensity (>50%) LDL-C reduction goal.⁴

Jonathon Firnhaber, MD
Greenville, NC

1. Cannon C, Blazing M, Giugliano R, et al. Ezetimibe added to statin therapy after acute coronary syndromes. N Engl J Med. 2015;372:2387-2397.

2. Savarese G, Ferrari G, Rosano G, et al. Safety and efficacy of ezetimibe: a meta-analysis. Int J Cardiol. 2015;201:247-252.

3. National Institute for Health and Care Excellence. Ezetimibe for treating primary heterozygous-familial and non-familial hypercholesterolaemia. Technology appraisal guidance [TA385]. February 24, 2016. www.nice.org.uk/guidance/ta385. Accessed September 12, 2018.

4. Goff DC Jr, Lloyd-Jones DM, Bennett G, et al. 2013 ACC/AHA guideline on the assessment of cardiovascular risk: a report of the American College of Cardiology/American Heart Association Task Force on Practice Guidelines. J Am Coll Cardiol. 2014;63:2935-2959.